A biosensor can be used to detect the presence of a specific antigen. These typically involve a sample of antibodies specific to the antigen of interest. There is a large class of biosensors that use immobilized antibodies on a surface as the sensing agent. The antibodies on the surface are identical and bind to a specific antigen, so that the sensor is specific to that particular antigen.
The antibody-antigen binding event must be detected. The traditional detection scheme in antibody sensors is fluorescence. In a typical sandwich assay, the immobilized antibody binds to the antigen; the system is then exposed to a fluorophore conjugated to the antibody, which then binds to the antigen. This tags the bound system upon exposure to light of a suitable wavelength.
The binding event also can be detected by the change in refractive index of the surface that occurs whenever antigens become bound to the antibodies on the surface. Such a biosensor is disclosed in U.S. Pat. No. 5,663,790, in which the bound antibodies are on a surface overlying an optical ring resonator. The change in refractive index shifts the resonant wavelength of the optical ring resonator. By sweeping the light frequency while observing the light intensity in the ring, the shift in resonant wavelength is observed, indicating a shift in refractive index and the corresponding event of the binding of the antigens to the antibodies.
One disadvantage of such a sensor is that the light source must have a variable wavelength that can be swept across a range. A related disadvantage is that the binding event can only be inferred after the light source wavelength has been swept across the range and the optical ring resonator response compared across the range. Another disadvantage is that the coupling between the change in refractive index in the sample and the detected optical output is limited because the sample is adjacent to and not within the optical ring interferometer. Finally, there appears to be no way of enhancing sensitivity of the sensor. The problem is that a very dilute antigen sample may not contain a sufficient population of antigens to bind to more than a small fraction of the bound antibodies, so that the change in refractive index may be so slight that the sensor cannot detect it.
What is needed is an optical sensor having an enhanced sensitivity capable of detecting extremely small changes in refractive index so as to be capable of sensing and measuring extremely weak or dilute antigen samples. Moreover, what is needed is a sensor that does not require expensive optical features such as a variable wavelength light source, and which does not require sweeping the light source wavelength across a range to make a measurement.